React trial ppt

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More Type Options. Sort By relevancy By date. Matching Exact phrase Include all of these words Include some of these words. First Name. In patients with acute coronary syndrome ACS , for whom an invasive evaluation is planned, prasugrel was associated with a 2. Stent thrombosis was rare in both groups, but numerically lower with prasugrel. Major bleeding rates were similar in both groups. Platelet inhibition using P2Y12 inhibitors in addition to aspirin is a cornerstone of contemporary therapy for acute coronary syndromes ACS.

The P2Y12 inhibitors most commonly utilized for patients presenting with ACS include clopidogrel, ticagrelor, and prasugrel. Whether ticagrelor or prasugrel is preferred over the other with regard to thrombotic and bleeding risk, however, remained unclear. At 1 year, prasugrel was associated with a 2. For the association between methylprednisolone and day mortality, the fixed-effect OR was 0.

The estimated associations between corticosteroids vs usual care or placebo and mortality in the subgroups defined by patient characteristics at randomization appear in Figure 3. Among critically ill patients, many more were receiving invasive mechanical ventilation at randomization patients and deaths than were not patients and 42 deaths. The overall fixed-effect OR was 0.

For comparison, the OR was 0. Among the 4 trials that recruited critically ill patients who were and were not receiving invasive mechanical ventilation at randomization, the association between corticosteroids and lower mortality was less marked in patients receiving invasive mechanical ventilation ratio of ORs, 4.

Among patients from 6 trials for whom data were available, For the association between corticosteroids and mortality, the OR was 1.

All trials contributed data according to age group and sex. For the association between corticosteroids and mortality, the OR was 0. For the association between corticosteroids and mortality based on data from 4 trials, the OR was 0.

In these trials, the study personnel were blinded to the intervention group. The associations between corticosteroids vs usual care or placebo and serious adverse events in each trial appear in Figure 4. Adverse events varied across trials but there was no suggestion that the risk of serious adverse events was higher in patients assigned to corticosteroids except for the 2 smallest trials, in which the total number of serious adverse events was 1 and 3.

In this prospective meta-analysis of 7 randomized clinical trials that included critically ill patients with COVID recruited from countries on 5 continents, administration of corticosteroids was associated with lower all-cause mortality at 28 days after randomization.

There was no suggestion of an increased risk of serious of adverse events. The ORs for the association between corticosteroids and mortality were similar for dexamethasone and hydrocortisone. The comparison of the association between low-dose corticosteroids and mortality and the association between high-dose corticosteroids and mortality was imprecisely estimated. Corticosteroids were associated with lower mortality among critically ill patients who were and were not receiving invasive mechanical ventilation at randomization, as well as in patients from the RECOVERY trial who required oxygen with or without noninvasive ventilation but were not receiving invasive mechanical ventilation at randomization.

These results were consistent with the subgroup analysis suggesting that the association between corticosteroids and lower mortality was stronger in patients who were not receiving vasoactive medication at randomization than in those who were receiving vasoactive medication at randomization.

The ORs for the association between corticosteroids and mortality appeared similar for older and younger individuals, men and women, and for longer and shorter durations of symptoms before randomization. Most ongoing trials of corticosteroids in critically ill patients with COVID suspended enrollment after these results became publicly available because equipoise for withholding corticosteroids was no longer present.

These trial results from diverse clinical and geographic settings suggest that in the absence of compelling contraindications, a corticosteroid regimen should be a component of standard care for critically ill patients with COVID The optimal dose and duration of treatment could not be assessed in this analysis, but there was no evidence suggesting that a higher dose of corticosteroids was associated with greater benefit than a lower dose of corticosteroids.

Inclusion of data from the Metcovid trial did not materially change the results other than reducing the inconsistency among the trials. Data from the Metcovid trial were not included in the primary meta-analysis because this trial was registered after the searches of the trial registries were conducted.

All subgroup analyses other than that comparing longer with shorter duration of symptoms at randomization were prespecified. Although the benefit associated with corticosteroids appeared greater in critically ill patients who were not receiving invasive mechanical ventilation at randomization, this comparison was based on only 4 trials and patients who were not receiving invasive mechanical ventilation at randomization, of whom 42 died.

Corticosteroids were associated with lower mortality in critically ill patients who were and were not receiving invasive mechanical ventilation at randomization, as well as in patients in the RECOVERY trial who required oxygen with or without noninvasive ventilation but were not receiving invasive mechanical ventilation at randomization.

These patients represented a spectrum of illness from patients receiving supplemental oxygen by nasal prongs to those receiving noninvasive ventilatory support in the form of high-flow oxygen or positive pressure by mask.

The findings from this prospective meta-analysis provide evidence that treatment with corticosteroids is associated with reduced mortality for critically ill patients with COVID The findings contrast with outcomes reported for the administration of corticosteroids among patients with influenza, for whom mortality and hospital-acquired infections may be increased by the administration of corticosteroids. However, serious adverse events were generally less likely in patients randomized to corticosteroids than to usual care or placebo.

This prospective meta-analysis was based on a relatively large number of critically ill patients with COVID from geographically diverse sites who were randomized to receive corticosteroids or to receive usual care or placebo. The protocol and analysis plan, including specification of subgroup analyses, was registered and made publicly available on the PROSPERO database prior to data analysis or receipt of outcome data.

The protocol also has been published along with a structured abstract. As is standard in meta-analyses, patients were compared only with other patients randomized in the same trial. Therefore, observed associations support a causal relationship between the administration of corticosteroids, compared with usual care or placebo, and reduced mortality. This study has several limitations. First, the prospective nature of this meta-analysis implies that there is little risk of selective reporting or of publication bias, 6 but it is possible that lack of participation by some investigators of ongoing trials was based on their knowledge of their trial results.

Nonetheless, the number of patients randomized in eligible trials who did not participate is likely to be smaller than the number of patients included in this meta-analysis.

It was the only trial that assessed the effect of methylprednisolone. Third, there were only limited missing outcome data, but in many trials, follow-up was censored when participants were discharged from the hospital. We are aware of no reason that the effect of corticosteroids on postdischarge day mortality would differ from that on predischarge mortality, but it will be important to report on longer-term mortality, including postdischarge mortality, in future analyses.

Fourth, the definitions and reporting of serious adverse events were not consistent across the trials and therefore a meta-analysis for this secondary end point was not conducted. Fifth, the trials only recruited adults, and the effect of corticosteroids on children remains unclear. Similarly, the trials were mainly conducted in high-income settings. Sixth, 1 trial reported mortality at 21 days and 1 trial reported mortality at 30 days after randomization, potentially leading to inconsistency between trial results.

In this prospective meta-analysis of clinical trials of critically ill patients with COVID, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower day all-cause mortality. Corresponding Author: Jonathan A. Published Online: September 2, Diaz, MD; Arthur S.

Marshall, MD. Author Contributions: Dr Sterne had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Slutsky reported being a co-primary investigator of one of the trials that is included in the meta-analysis. Dr Angus reported receiving personal fees from Ferring Pharmaceuticals Inc, Bristol-Myers Squibb, Bayer AG, and Alung Technologies Inc; and having patents pending for Selepressin compounds, compositions, and methods for treating sepsis and for proteomic biomarkers of sepsis in elderly patients.

Dr Emberson reported receiving grants from Boehringer Ingelheim. Dr Lim reported receiving grants from Pfizer. No other disclosures were reported. This group assembled information on ongoing trials and invited trial investigators to participate in this prospective meta-analysis. The WHO chief scientist invited trial investigators to participate and provided a secure portal for submission of data. Other than the contributions of Dr Diaz as a coauthor, the WHO had no role in the preparation, review, or approval of the manuscript.

The WHO had no role in the decision to submit the manuscript for publication. Dr Angus is Associate Editor, JAMA , but was not involved in any of the decisions regarding review of the manuscript or its acceptance. Additional Contributions: We gratefully acknowledge the efforts of all trial investigators the lists of names appear in the Supplement and the patients who provided consent for participation. We thank Agnes Sagfors, PhD, and other staff at the W 2 O Group for searches of trial registries and for administrative and communications support.

None of these persons received compensation beyond their usual salaries. Our website uses cookies to enhance your experience.

By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue. Download PDF Comment. Figure 1. View Large Download.

Figure 2. Figure 3. Figure 4. Table 1. Characteristics of Included Trials. Table 2. Characteristics of Patients Included in the Prospective Meta-analysis. Conversations with Dr Bauchner Subscribe to Podcast. Lists of investigators and steering committee eTable 1. Summary of assessments of the risk of bias in the estimated effect of corticosteroids on mortality and serious adverse events in each trial, with brief explanation of judgements eTable 2.

Effects of corticosteroids on day mortality according to whether patients received invasive mechanical ventilation IMV at the time of randomization eFigure 2. Effects of corticosteroids on day mortality according to whether patients received vasoactive medication at the time of randomization eFigure 3.

Corticosteroids and infectious diseases. PubMed Google Scholar Crossref. Corticosteroids in the treatment of severe sepsis and septic shock in adults. Corticosteroids for treating sepsis in children and adults.

PubMed Google Scholar. Clinical evidence does not support corticosteroid treatment for nCoV lung injury. Rationale for prolonged corticosteroid treatment in the acute respiratory distress syndrome caused by coronavirus disease Chapter prospective approaches to accumulating evidence. Accessed August 24, Dexamethasone in hospitalized patients with Covid—preliminary report.

Published online July 17, Published online August 24, Acute respiratory distress syndrome: the Berlin definition. Effect of hydrocortisone on day mortality or respiratory support among critically ill patients with COVID a randomized clinical trial. Published online September 2, RoB 2: a revised tool for assessing risk of bias in randomised trials.

GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency CIRCI in critically ill patients part I. Consensus values and weighting factors. Comparative performance of heterogeneity variance estimators in meta-analysis. A refined method for the meta-analysis of controlled clinical trials with binary outcome.

The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method. Meta-analytical methods to identify who benefits most from treatments.

Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID the CoDEX randomized clinical trial. Accessed August 11, Published online August 12, Rate of intensive care unit admission and outcomes among patients with coronavirus.

Corticosteroids as adjunctive therapy in the treatment of influenza. This randomized clinical trial compares the effect of low-dose hydrocortisone vs placebo on treatment failure death or persistent respiratory support dependency at 21 days in critically ill patients with COVID and acute respiratory failure in France. This open label clinical trial compares the effects of dexamethasone vs usual care on the number of days alive and free of mechanical ventilation at day 28 among COVID patients in Brazil with moderate to severe acute respiratory distress syndrome ARDS.

Bruno M.